Pedro Gonzalez

Associate Professor of Ophthalmology

I am interested in understanding the pathologic changes that take place in the trabecular meshwork (the tissue in the eye that is hydrodynamically abnormal in glaucoma). My work is based on the general hypothesis that different types of stress affecting the cells of the trabecular meshwork lead to the accumulation of damage in such cells over many years. This results in loss of cellularity and increase in the number of non-functional cells characterized by a senescent phenotype.

Specifically I am interested in the three following subjects related to this hypothesis:

- Understanding the mechanisms by which proteasome inhibition leads to cellular senescence.
Recently it has been shown that inhibition of the proteasome triggers a senescent phenotype in fibroblasts. It is not clear at this point what signaling mechanisms are involved in triggering the program for cellular senescence. I am currently working in determining if proteasome inhibition results in cellular senescence in the cells of the outflow pathway, and in the identification of the mechanisms involved in this process.

- Characterizing the role of the cytokines TGF-beta-1 and TGF-beta-2 in accelerating the degenerative process of the trabecular meshwork.
There is evidence that the concentration of the active form of the cytokine TGF-beta-2 is increased in the aqueous humor of patients with primary open angle glaucoma. We have also found that mechanical stress induces the production of TGF-beta-1 in the cells of the trabecular meshwork. Both cytokines have the potential to generate pathologic effects at long term in the outflow pathway, including fibrosis, loss of cellularity, cellular senescence, and cell growth arrest. I am currently studying the effects of chronic exposure to TGF-beta-2 in the trabecular cells using a recombinant adenovirus expressing the constitutively active form of the protein.

- Studying the dynamics of cell turnover in the trabecular meshwork and the role of the Schwalbe line's cells as progenitor cells.
There is increasing evidence for the presence of either progenitor or stem cell populations in adult tissues. These cells are believed to play an important role in the maintenance and regeneration of their specific tissues, and the decline of their activity has been hypothesized to be a major factor in the progression aging and age related disease. Analysis of cell division after laser trabeculoplasty point at the cells of the Schwalbe's line as potential progenitor of the trabecular meshwork. We have recently identified positive and negative markers for these cells as well as the presence of colony-forming cells in primary cultures that shear these markers. I am interested in studying the role of Schwalbe line's cells in maintaining a normal population of cells in the trabecular meshwork as well as studying the possibility that a decline in the function of these cells may play a role in glaucoma.

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